Fingolimod is a sphingosine-1 phosphate (S1P) agonist, having immunosuppressive activity. Fingolimod, in the form of its hydrochloride salt has the following formula:

Fingolimod is currently marketed as an immediate release capsule for the treatment of multiple sclerosis. This formulation contains 0.5 mg equivalent of fingolimod base in the form of the hydrochloride salt.
WO2010/055028, US 20100040678, US 20060275357, US20090203798, US20080311188, WO2009/48993 disclose formulations containing inter alia fingolimod.
WO2010/055028 discloses crystalline forms and hydrates of fingolimod hydrochloride and pharmaceutical formulations thereof. The solid pharmaceutical formulations comprise the crystalline fingolimod hydrochloride and a sugar alcohol. The sugar alcohol can be, e.g. mannitol, maltitol, inositol, xylitol or lactitol.
US 20100040678 discloses rapidly disintegrating dosage forms of S1P agonists including FTY720 (fingolimod). The compositions comprise a coating, wherein the coating comprises one or more polymer resins and one or more metal oxides.
US 20060275357, US20080311188 and US20090203798 disclose pharmaceutical compositions of S1P agonists comprising a sugar alcohol, such as mannitol.
WO2009/048993 discloses dosage forms containing S1P modulators and one or more excipients selected from fillers, binders, disintegrants, lubricants, flow regulators, matrix formers, plasticizers, flavouring agents and sweeteners.
The applicant has discovered that certain S1P agonist compounds, and in particular, fingolimod, possess properties that can cause processing problems when preparing pharmaceutical formulations. In particular, it has been found that fingolimod particles have a strong tendency to stick to surfaces and to each other. Moreover, the applicant has found that there is a significant problem with achieving a desirable content uniformity in pharmaceutical formulations containing fingolimod. Further, fingolimod can react with certain excipients to produce degradation products in the final formulation. The present invention addresses the need to provide stable formulations of fingolimod that additionally have a desirable content uniformity by a simplified process.
The applicant has found that the stability and uniformity of pharmaceutical compositions containing fingolimod is heavily dependent on the choice of excipients used in the formulation, and the process by which the formulation is prepared.